Validation techniques for fluid delivery systems

ABSTRACT

A fluid delivery system may include a container that houses a medical fluid, a fluid pressurizing unit, and a fluid transfer set that transfers the medical fluid from the container to the fluid pressurizing unit. To validate the integrity and sterility of the fluid delivery system, the system may undergo testing protocols to evaluate the susceptibility of the system to pathogenic ingress, chemical degradation, and/or fluid cross-contamination between patient fluid delivery procedures. The testing protocols may help ensure that delivery system components used during multiple different fluid delivery procedures perform as well as if the components were replaced after each fluid delivery procedure.

CROSS-REFERENCE

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/733,825, filed Dec. 5, 2012, the entire contents of which areincorporated herein by reference.

TECHNICAL FIELD

This disclosure relates to medical fluid containers and, moreparticularly, to medical fluid containers for medical fluid deliverysystems.

BACKGROUND

Various medical procedures require that one or more medical fluids beinjected into a patient. For example, medical imaging proceduresoftentimes involve the injection of contrast media into a patient,possibly along with saline and/or other fluids. Contrast media canhighlight features that would otherwise be less distinguishable fromnearby tissue to help a clinician diagnose and treat a patient's medicalcondition. A patient is typically injected with contrast media before orduring an imaging procedure and then exposed to radiation orelectromagnetic energy to generate an image of the patient's body.

When used, contrast media is usually injected into a patient by anautomated injection system. The automated injection system may include apump, syringe, or other fluid delivery device operatively connected to acatheter. The catheter is placed into a vein or artery of a patient.During operation, the fluid delivery device operates to pressurize thecontrast media and to inject the media into the patient at apredetermined rate and volume.

Contrast media for an automated injection system can be supplied in acontainer sized to provide multiple doses of contrast media to multipledifferent patients or a container sized to provide a single dose ofcontrast media to a single patient. For example, a powered syringeinjector may use a pre-filled syringe that is filled with fluid at onefacility and then shipped to another facility (e.g., an imaging suit)where it is installed on the powered injector. In this case, the syringeis used for a single injection on a single patient. Any contrast mediaremaining in the syringe after this single injection cannot be used foranother patient and is thereby wasted.

Alternatively, a powered syringe injector may receive an empty syringe(e.g., in an imaging suite) that is filled with fluid from a multi-dosecontainer in preparation for subsequent injection into a patient. Thesyringe in this application may or may not still only be used for asingle injection on a single patient. However, the multi-dose containersupplying fluid to the syringe and tubing connecting the container tothe syringe may be used to fill multiple syringes for multiple differentpatients. Ensuring that contaminants do not enter the fluid supplied bythe multi-dose container between syringe fillings or during syringefilling may be beneficial for the safe and efficient operation of theautomated injection system.

SUMMARY

In general, this disclosure is directed to systems and techniques forevaluating the integrity and sterility of components in a fluid deliverysystem (e.g., a fluid injector system). The fluid delivery systemincludes, for example, a medical fluid container, a fluid pressurizingunit, and a fluid transfer set. The disclosed techniques can be used tohelp validate and ensure that the components of the fluid deliverysystem do not allow ingress of pathogens; do not chemically degradeduring use; and/or do not allow cross-contamination of fluids betweenpatients during subsequent injection procedures. By following structuredprotocols, suppliers of fluid delivery system components can benchmarktheir compliance and determine if redesign of injector system componentsis necessary. Further, fluid delivery system validation can allowsuppliers, clinicians, and patients to all proceed with confidence inthe knowledge that the injection system hardware meets standards forintegrity.

In one example, a method is described that includes applying pathogen ata connection between a medical fluid container, a fluid pressurizingunit, and a fluid transfer set. The fluid transfer set is configured toprovide fluid communication between the medical fluid container and thefluid pressurizing unit. The method also includes determining if thepathogen enters a medical fluid in at least one of the medical fluidcontainer, the fluid pressurizing unit, and the fluid transfer set.Additionally, the method involves holding the medical fluid in the fluidtransfer set and the fluid pressurizing unit, and evaluating the fluidto determine if chemical degradation has caused these components torelease particles or leach chemicals into the medical fluid.

In another example, a method is described that includes applying abacteria to a connection between a medical fluid container and a fluidtransfer set, where the fluid transfer set is connected to transfer afluid from the medical fluid container to a fluid pressurizing unit. Themethod also includes applying the bacteria to a connection between thefluid transfer set and the fluid pressurizing unit, and drawing thefluid from the medical fluid container, through the fluid transfer set,and into the fluid pressurizing unit. The example method furtherinvolves extracting a sample of the fluid from the fluid pressurizingunit, and analyzing the sample to determine a concentration level of thebacteria in the sample.

In another example, a method is described that includes providing afluid delivery system that includes a medical fluid container, a fluidpressurizing unit, and a fluid transfer set, where the fluid transferset is connected to transfer a fluid from the medical fluid container tothe fluid pressurizing unit. The method includes drawing the fluid fromthe medical fluid container, through the fluid transfer set, and intothe fluid pressurizing unit so that the fluid transfer set and fluidpressurizing unit are filled with the fluid, and holding the fluid inthe fluid transfer set and the fluid pressurizing unit for a period oftime. In addition, the method involves extracting a sample of the fluidfrom at least one of the fluid transfer set and the fluid pressurizingunit, analyzing the sample to determine if chemical degradation of theat least one of the fluid transfer set and the fluid pressurizing unitcaused release of particles or leaching of chemicals into the sample.

In another example, a method is described that includes providing afluid delivery system that includes a medical fluid container, a fluidpressurizing unit, and a fluid transfer set, where the fluid transferset is connected to transfer a fluid from the medical fluid container tothe fluid pressurizing unit. The method includes drawing the fluid fromthe medical fluid container, through the fluid transfer set, and intothe fluid pressurizing unit so that the fluid transfer set and fluidpressurizing unit are filled with the fluid. Additionally, the methodincludes placing a discharge outlet of the fluid pressurizing unit influid communication with a fluid reservoir containing a tracking fluid,where the tracking fluid contains a tracking agent, and where the fluidreservoir is closed so that the fluid pressurizing unit cannot draw thefluid from the medical fluid container and discharge the fluid into thefluid reservoir. The example method further involves operating the fluidpressurizing unit so as to pressurize a portion of the fluid in thefluid pressurizing unit, extracting a sample of the fluid from at leastone of the medical fluid container, the fluid transfer set, and thefluid pressurizing unit, and analyzing the sample to determine aconcentration of the tracking agent in the at least one of the medicalfluid container, the fluid transfer set, and the fluid pressurizingunit.

In another example, a method is described that includes providing afluid delivery system that includes a medical fluid container, a fluidpressurizing unit having a discharge outlet, a fluid transfer set, and adischarge line. The fluid transfer set is connected to transfer a fluidfrom the medical fluid container to the fluid pressurizing unit, and thedischarge line is connected to the discharge outlet of the fluidpressurizing unit. The method includes filling the discharge line with atracking agent, establishing a positive pressure that biases thetracking agent in the discharge line toward the fluid pressurizing unit,and extracting a sample of the fluid from at least one of the medicalfluid container and the fluid transfer set. The example method alsoincludes analyzing the sample to determine a concentration of thetracking agent in the at least one of the medical fluid container andthe fluid transfer set.

In another example, a method is described that includes applying abacteria to a connection located between a medical fluid container and afluid pressurizing unit, where a fluid transfer set is configured totransfer a fluid from the medical fluid container to the fluidpressurizing unit. The method includes operating the fluid pressurizingunit multiple times to discharge multiple portions of fluid from thefluid pressurizing unit and obtaining a plurality of samples from themultiple portions of fluid discharged from the fluid pressurizing unit,each of the plurality of samples being obtained from a different portionof fluid. The method also includes analyzing the plurality of samples todetermine a concentration level of the bacteria in the plurality ofsamples.

Products validated using one or more method according to the disclosureare also described. For example, a validated kit may include a validatedmedical fluid container, a validated fluid transfer set, and/or avalidated fluid pressurizing unit. The products may be validated forresistance to bacterial entry into a medical fluid held in the medicalfluid container and transferred through the fluid transfer set via thefluid pressurizing unit. The products may additionally or alternativelybe validated for chemical compatibility with a medical fluid. In oneexample, the medical fluid is a contrast medium.

The details of one or more examples are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a function block diagram illustrating components of an examplefluid delivery system.

FIG. 2 is an illustration of an example configuration of a fluidtransfer set that may be used in the example fluid delivery system ofFIG. 1.

FIG. 3 is an illustration of another example configuration of a fluidtransfer set that may be used in the example fluid delivery system ofFIG. 1.

FIG. 4 is a cross-sectional illustration of an example mechanicalconnector that can be used in the example fluid delivery system of FIG.1.

FIGS. 5A, 5B, 6, 7A, and 7B are flow diagrams illustrating exampletechniques that may be performed to validate the integrity and sterilityof the example fluid delivery system of FIG. 1.

FIGS. 8A and 8B are perspective drawings of an example peristaltic pumpthat has a fluid seal and may be used as a fluid pressurizing unit.

FIG. 9 is a perspective drawing of the peristaltic pump of FIGS. 8A and8B illustrating a discharge line filled with a tracking agent.

DETAILED DESCRIPTION

The following detailed description is exemplary in nature and is notintended to limit the scope, applicability, or configuration of theinvention in any way. Rather, the following description providespractical illustrations for implementing exemplary embodiments of thepresent invention. Examples of constructions, materials, dimensions, andmanufacturing processes may be provided for selected elements, and allother elements employ that which is known to those of skill in the fieldof the invention. Those skilled in the art will recognize that many ofthe examples provided have suitable alternatives that can be utilized.

A powered medical fluid injector may be used to inject a medical fluidsuch as contrast media into the body of a patient during a diagnosticimaging procedure. To perform an injection, the medical fluid injectoris supplied with one or more desired medical fluids. The medical fluidinjector pressurizes the medical fluid and discharges the pressurizedfluid into a catheter inserted into the patient. By controlling thetype, rate, and volume of medical fluid delivered to the patient, aclinician can control the visual contrast of structures or fluids withinthe patient to help the clinician diagnose and treat the patient'smedical condition.

A medical fluid injector can be supplied with medical fluid from anumber of different sources. Depending on the configuration of theinjector and type of fluid intended to be injected, the injector can besupplied with a single dose of fluid that is used only for a singlepatient. For example, when the medical fluid injector is configured as asyringe injector, a syringe prefilled with medical fluid by a medicalfluid manufacturer or supplier may be loaded into the injector. Afterinjecting the fluid from the syringe, the syringe may be removed andreplaced with another prefilled syringe for a different patient. Theempty syringe can be discarded or sent back to the medical fluidmanufacturer or supplier for refilling and sterilization, as required.

Alternatively, rather than send a facility housing a medical fluidinjector a syringe prefilled with fluid, a medical fluid manufacturer orsupplier may instead send the facility a bulk container holding enoughmedical fluid for multiple patients. At the facility, personnel mayconnect the bulk container directly to the medical fluid injector or mayinstead connect the bulk fluid container to an injector reservoir (e.g.,an empty syringe) that is filled and then loaded into the medical fluidinjector. In either case, the bulk fluid container can supply enoughmedical fluid to inject multiple different patients with the fluidduring different imaging procedures.

When a medical fluid injector is configured to receive fluid from a bulkmedical fluid container, the injector can be connected to a multi-usetubing set that transfers the medical fluid from the container to theinjector and a patient-specific tubing set that transfers the medicalfluid from the injector to a specific patient. The multi-use tubing setmay be used during injection procedures for multiple patients, althoughthe tubing set may nevertheless be replaced on a periodic basis (forexample, once per day or one per shift). The patient-specific tubingset, by contrast, may be replaced between patient injection proceduresso that there is a new tubing set for each new patient.

Components used multiple times in a medical fluid injector system withdifferent patients cannot become contaminated or lose sterility duringany one injection procedure. This is because components contaminated orthat have lost sterility during one injection procedure may causecross-contamination between patients, compromising the integrity of theinjection system. For example, if contaminants enter a bulk medicalfluid container during an injection of one patient, the contaminants mayremain in the fluid during injection of subsequent patients.

To help ensure that components used in a medical fluid injector systemduring multiple different injection procedures do not present a risk ofcross-contamination between patients, the injector system andconstituent components can be tested to validate their ability to resistcross-contamination and loss of sterility. For example, the injectorsystem and constituent components may be tested prior to any patientinjection procedures to validate that the system and components will notlose safety or integrity during the course of multiple differentinjection procedures.

In accordance with some examples of the present disclosure, systems andtechniques are described for testing multi-use medical fluid injectorsystem hardware to validate that the hardware does not becomecontaminated or otherwise lose chemical or biological safety orintegrity during the course of injecting multiple different patientswith medical fluid. The testing may validate that the multi-use hardwaredoes not degrade during the course of multiple injection proceduresand/or does not provide a pathway that can allow contaminants to enterthe system and to transfer from one patient to another patient duringexpected use.

Example techniques for validating the safety and integrity of injectorsystems and their constituent components will be described in greaterdetail with reference to FIGS. 5-9. Further, example components that maybe included in a medical fluid injector system will be described withreference to FIGS. 2-4. However, an example medical fluid deliverysystem will first be described with reference to FIG. 1.

FIG. 1 is a function block diagram illustrating components of a fluiddelivery system 10, which includes a powered fluid injector 12, amedical fluid container 14 (hereinafter “container 14”), and a fluidtransfer set 16 fluidly connecting powered fluid injector 12 to medicalfluid container 14. Powered fluid injector 12 includes a fluidpressurizing unit 18, a motor 22, a processor 24, and a memory 26. Motor22 is operatively coupled to fluid pressurizing unit 18 and configuredto drive the fluid pressurizing unit to draw a medical fluid fromcontainer 14 and pressurize the fluid for discharge into a patientduring an imaging procedure. Processor 24 is communicatively coupled tomotor 22 and memory 26. In the example of FIG. 1, fluid pressurizingunit 18 defines a discharge outlet 28 that in fluid communication with apatient catheter 32 via a patient line or extension tube 30.

Fluid delivery system 10 may include one or more multi-use componentsthat are used repeatedly during the course of multiple patientinjections. For example, container 14 and fluid transfer set 16 may beused during the course of multiple patient injections and may only bereplaced on a periodic basis. By contrast, one or more other componentsof fluid delivery system 10 may be patient-specific, single usecomponents that are replaced for each patient injection procedure. Forexample, patient line 30 and catheter 32 may be replaced for each newpatient receiving an injection using powered fluid injector 12. Fluidpressurizing unit 18 in powered fluid injector 12 may or may not also bereplaced for each new patient.

In instances in which fluid delivery system 10 includes one or moremulti-use components, the multi-use components cannot lose theirintegrity or provide pathways for contamination during their servicelife in the fluid delivery system. Testing the components in fluiddelivery system 10 can validate the safety and integrity of thecomponents for extended service during multiple injection procedures formultiple patients. Although different tests can be performed, in oneexample as will be described in greater detail below, the components aretested by challenging the connection or joints between components with apathogen (e.g., bacteria and/or virus) and then evaluating whether thepathogen is able to enter a medical fluid in fluid delivery system 10 atthe connection or joints. In another example, the components of fluiddelivery system 10, including fluid transfer set 16 and pressurizingunit 18, are filled with a medical fluid that is then allowed to residein the components for a period longer than components would be filledduring a single patient injection. The medical fluid and/or componentsare then evaluated to determine if the components degrade and releaseparticles or leach chemicals into the medical fluid. In yet anotherexample, pressurizing unit 18 is operated to discharge medical fluidagainst a blocked fluid outlet containing a tracking agent. Such anoperation may simulate injecting medical fluid into a patient with ablocked catheter. Additionally or alternatively, a discharge lineconnected to pressurizing unit 18 may be filled with a tracking agentand placed under a pressure that tends to force the tracking agent backinto the pressurizing unit. In either example, a medical fluid in fluidcommunication with pressurizing unit 18 during testing with the trackingagent can be evaluated to determine if the tracking agent is present inthe medical fluid, which may indicate backflow of fluid from apatient-specific line into a multi-use component. In this way theoperational integrity of fluid delivery system 10 may be analyzed andvalidated.

During operation of powered fluid injector 12, pressurizing unit 18receives a medical fluid from container 14, pressurizes the medicalfluid, and discharges the pressurized medical fluid through dischargeoutlet 28 and into catheter 32. Pressurizing unit 18 can be anymechanism configured to increase the pressure of a liquid medical fluidfor injection into a patient. Depending on the configuration ofpressurizing unit 18, the unit may pressurize the medical fluid so itdischarges through discharge outlet 28 at a pressure greater than 50pounds per square inch (psi) such as, e.g., a pressure greater than 200psi, a pressure greater than 500 psi, or even a pressure greater than1000 psi.

In one example, pressurizing unit 18 is implemented as a syringe. Thesyringe may include a syringe barrel that receives and holds medicalfluid from container 14 and a plunger that is disposed within andmoveable relative to the syringe barrel. To fill the syringe, thesyringe may be fluidly coupled to container 14 and the syringe plungerdriven to its furthest forward position adjacent discharge outlet 28.This will expel the majority of the air that is located within thesyringe. Thereafter, the plunger is retracted within the syringe barrel,creating a vacuum within the syringe barrel that draws medical fluidfrom container 14 and into the syringe barrel. To subsequently dischargethe medical fluid, fluid communication between the syringe barrel andcontainer 14 is closed, and the plunger is advanced forward in thesyringe barrel to pressurize and discharge the medical fluid in thesyringe barrel.

In another example, pressurizing unit 18 is implemented as a pump. Thepump may draw fluid from container 14 and discharge the fluid under anincreased pressure out of discharge outlet 28. When pressurizing unit 18is implemented as a pump, the pump may be an axial pump, a centrifugalpump, a pusher plate pump, a piston-driven pump, or other pumpingdevice. In one such example (e.g., FIGS. 8A, 8B, and 9), the pump is asqueeze pump that squeezes a compressible fluid tube (e.g., a plastictube) in a controlled manner, e.g., such as a peristaltic pump, toprogressively pressurize and move medical fluid through the tube.

While powered fluid injector 12 in the example of FIG. 1 is illustratedas having only a single pressurizing unit 18, in other examples, thepowered injector system may have multiple pressurizing units. Forexample, in addition to pressurizing unit 18 receiving fluid fromcontainer 14, powered fluid injector 12 may include one or moreadditional pressurizing units that can receive fluid from container 14or a different medical fluid container (not illustrated). For instance,powered fluid injector 12 may include pressurizing unit 18 that receivesfluid from container 14 holding one type of medical fluid and anotherpressurizing unit that receives fluid from a different container holdinga different type of medical fluid. When powered fluid injector 12includes multiple pressurizing units, each pressurizing unit may be thesame type (e.g., each pressurizing unit is a syringe or pump) or thepressurizing units may be of different types.

Motor 22 is operatively coupled to pressurizing unit 18 and may providemechanical energy that causes the pressurizing unit to draw medicalfluid from container 14 and to pressurize the medical fluid fordischarge out through discharge outlet 28. In one example, motor 22 is aDC motor that is configured to advance and retract a plunger through asyringe barrel. In another example, motor 22 is a DC motor that isconfigured to drive a pump head. Regardless, motor 22 may or may not bea variable speed motor that can ramp up speed and ramp down speed tocontrol the rate at which pressurizing unit 18 delivers medical fluid toa patient.

During operation, powered fluid injector 12 receives medical fluid fromcontainer 14. Container 14 may be a bottle, a bag, or any other suitablecontainer that is configured to hold and store a liquid fluid. Container14 is typically formed from plastic or glass, although any suitablematerials can be used to fabricate container 14. Depending on theapplication, container 14 may be sized to hold enough liquid to injectonly a single dose of the liquid into a single patient or enough liquidto inject multiple doses of the liquid into multiple different patients.When container 14 is sized to hold only a single dose of liquid for asingle patient, the container may, for example, hold a volume less thanapproximately 100 milliliters (ml). By contrast, a container sized tohold enough liquid to inject multiple doses of the liquid into multipledifferent patients may hold more liquid that fluid pressurizing unit 18can hold when fully filled. In some examples when container 14 is sizedto hold enough liquid to inject multiple doses, the container may holdgreater than approximately 100 ml such as, e.g., greater than or equalto 200 ml, greater than or equal to 300 ml, or greater than or equal to500 ml. The foregoing volumes are merely examples, and it should beappreciated that the disclosure is not limited in this respect.

Container 14 can contain a wide variety of different fluids such ascontrast media, flushing agents (e.g., saline), and fluid medications,among others. Contrast media is a liquid that can be injected into apatient to highlight selected areas of the patient while the patient isbeing scanned, e.g., radiographically. Contrast media typically has aviscosity ranging from approximately 1 centipoise to approximately 50centipoise and, in some examples, may have an organically (i.e.,non-ionic) or non-organically (i.e., ionic) bound molecule thatfunctions to provide contrast, such as organically or non-organicallybound iodine. Examples of iodine-based contrast media includediatrizoate (Hypaque™ 50), metrizoate (Isopaque 370), ioxaglate(Hexabrix), iopamidol (Isovue® 300, Isovue® 370), iohexol (Omnipaque™350), ioxilan (Oxilan® 350), iopromide (Ultravist® 370), and iodixanol(Visipaque™ 320). Other example contrast media agents includebarium-based agents such as barium sulfate. In still other examples,contrast media may include gadolinium for MR imaging, radioisotopes fornuclear medicine, micro-spheres for ultrasound, or the like.

Although fluid delivery system 10 is only illustrated as including asingle container 14 of medical fluid, fluid delivery system 10 mayinclude multiple containers that can each house the same medical fluidor that can house different medical fluids. In one example, fluiddelivery system 10 includes at least two containers that each house thesame contrast medium, increasing the amount of fluid connected topressurizing unit 18 for injecting into patients as compared to whenthere is only a single reservoir. In another example, fluid deliverysystem 10 includes at least two containers where one container houses acontrast medium and another container houses a flushing media such assaline. Powered fluid injector 12 may inject alternating doses of thecontrast medium and the saline into a patient to control the patient'sresponse to the contrast medium during imaging.

To transfer medical fluid from container 14 to pressurizing unit 18,fluid delivery system 10 includes fluid transfer set 16. Fluid transferset 16 may provide a fluid communication pathway between container 14and pressurizing unit 18. Fluid transfer set 16 may include a segment oftubing (e.g., flexible polymeric tubing) or duct that allows fluid to beconveyed from container 14 to fluid pressurizing unit 18. In theillustrated example, fluid transfer set 16 extends from a proximal end34 that connects to container 14 to a distal end 36 that connects topressurizing unit 18. In such an example, fluid transfer set 16 maydefine at least one connection between the fluid transfer set andcontainer 14 and another connection between the fluid transfer set andpressurizing unit 18. The connections may be locations where onecomponent (e.g., container 14) is joined to another component (e.g., aflexible tube) to form a junction. The specific number of connectionsbetween container 14 and pressurizing unit 18 may vary depending on thespecific configuration of fluid transfer set 16. Further, depending onthe configuration, each of the connections may be detachable connectionsrather than permanent connections to allow an operator to exchange andreplace components. In addition, depending upon the design of fluidinjector 12, transfer set 16 may interface with an ultrasonic orelectro-optic sensor to detect fluid presence in the tube. This canserve the dual purpose of preventing air entry into the pressurizingunit by allowing the operator to have an automatic container 14 emptydetection.

To connect proximal end 34 of fluid transfer set 16 to container 14, thefluid transfer set may have a mechanical connector positioned atproximal end 34. The mechanical connector may be a threaded male orfemale connector that is configured to mate with a correspondingconnector on container 14. For example, fluid transfer set 16 may have afemale or male luer lock fitting positioned at proximal end 34 that isconfigured to engage with a corresponding luer lock fitting on container14 for creating a fluid tight connection between the components.Alternatively, as described with respect to FIG. 4, fluid transfer set16 may have a bottle spike positioned at proximal end 34 for piercing aseal on container 14 when placing the container in service.

Distal end 36 of fluid transfer set 16 may also have a mechanicalconnector for connecting to pressurizing unit 18. For example, as withthe connector on proximal end 34, the mechanical connector on distal end36 may be a threaded male or female connector that is configured to matewith a corresponding connector on container 14. In one example, fluidtransfer set 16 has a female or male luer lock fitting positioned atdistal end 36 that is configured to engage with a corresponding luerlock fitting on pressurizing unit 18 for creating a fluid tightconnection between the components. In addition, although distal end 36of fluid transfer set 16 is described as connecting to pressurizing unit18, it should be appreciated that the fluid transfer set may not connectto the pressurizing unit directly but may instead connect throughintermediary structures. For example, distal end 36 of fluid transferset 16 may connect to a valve assembly that controls fluid communicationbetween container 14 and pressurizing unit 18 which, in turn, is influid communication with the pressurizing unit.

In the example of FIG. 1, pressurizing unit 18 is simultaneouslyconnected to container 14 and catheter 32 through separate fluid ports.In other examples, pressurizing unit 18 may have a single fluid portthat is connected at separate times to container 14 and catheter 32. Forexample, during a fill operation, pressurizing unit 18 may be connectedto container 14. Once pressurizing unit 18 has been filled with asuitable amount of fluid, the pressurizing unit may be disconnected fromcontainer 14 and connected to catheter 32, thereby allowing a singlefluid port to function as both a fluid filling inlet and a fluiddischarge outlet.

During operation of powered fluid injector 12, processor 24 may controlthe filling of medical fluid to and discharge of medical fluid frompressurizing unit 18 with the aid of instructions associated withprogram information stored in memory 26. Processor 24 may also controlthe filling of medical fluid to and discharge of medical fluid frompressurizing unit 18 based on instructions received from a user, e.g.,via a user interface. Instructions executed by processor 24 may, forexample, define fluid delivery programs that specify the quantity, rate,and/or pressure with which medical fluid is to be delivered frompressurizing unit 18 through discharge outlet 28 during a diagnosticimaging procedure and/or during operational testing of powered fluidinjector 12. Instructions executed by processor 24 may also control theopening and closing of valves within fluid delivery system 10 (notillustrated) to fill pressurizing unit 18 with medical fluid and todischarge the fluid from the unit.

Processor 24 may include one or more processors, such as one or moremicroprocessors, digital signal processors (DSPs), application specificintegrated circuits (ASICs), field programmable gate arrays (FPGAs),programmable logic circuitry, or the like, either alone or in anysuitable combination. In general, processor 24 may receive electricalsignals from input devices such as a user interface and provideelectrical signals to output devices such as motor 22. For example,processor 24 may provide signals to motor 22 to control the advancingand retracting of a plunger in a syringe barrel and/or the movement of apump head. Memory 26 may store instructions and related data that, whenexecuted by processor 24, cause powered fluid injector 12 and processor24 to perform the functions attributed to them in this disclosure.Typically, powered fluid injector 12 uses electrical energy to drivepressurizing unit 18, although hydraulic, pneumatic, or other suitablepower sources may also be used.

In the example of FIG. 1, fluid pressurizing unit 18 defines a dischargeoutlet 28 that is in fluid communication with a patient catheter 32 viaa patient line 30. Patient line 30 may also be referred to as adischarge line, e.g., when the line is not connected to catheter 32outside of a patient injection procedure. Discharge outlet 28 may be anopening in fluid pressurizing unit 18 through which high pressure fluidis discharged and may or may not include a length of tubing (e.g.,patient line 30 or another line) connected to the outlet. Patient line30 may be a length of tubing that traverses from powered fluid injector12 to catheter 32 and can comprise a unitary tube or a plurality of tubesegments connected together to form an overall length of tube. In otherexamples, catheter 32 may be coupled directly to fluid pressurizing unit18 without the aid of intermediate tubing or extensions.

Fluid delivery system 10 can be used in any appropriate applicationwhere delivery of one or more medical fluids is desired including, forexample, during any type of medical imaging procedure. Example imagingprocedures in which fluid delivery system 10 can be used include, butare not limited to, X-ray, computed tomography (CT), nuclear magneticresonance (NMR)/magnetic resonance (MR), ultrasound, fluoroscopy, andpositron emission tomography (PET). When used in these applications,powered fluid injector 12 may be communicatively coupled to an imagingsystem (e.g., a CT scanner) and may send and receive electrical signalsbetween the imaging system for controlling the operation of the fluiddelivery device.

As discussed above, fluid delivery system 10 can have a variety ofdifferent configurations to transfer fluid from container 14 to fluidpressurizing unit 18 and, ultimately, catheter 32. FIG. 2 illustratesone example configuration of a fluid transfer set 40 that may be used asfluid transfer set 16 in fluid delivery system 10. Fluid transfer set 40includes a length of flexible polymeric tubing 42 that extends from aproximal end 44 to a distal end 45. A mechanical connector 46 is locatedat proximal end 44 and is configured to mate with container 14 so as tocreate a fluid tight connection between the container and fluid transferset 40. Mechanical connector 46 includes a base 48 that is configured toreceive and mate with a rim of container 14 that extends around anopening through which medical fluid is withdrawn from the container.Mechanical connector 46 also includes a spike 50 that projectsproximally away from base 48. As described in greater detail withrespect to FIG. 4, spike 50 is configured to be inserted into container14 and to pierce a seal on the container so as to place the container influid communication with fluid transfer set 40.

Fluid transfer set 40 in the example of FIG. 2 also includes amechanical connector 52 located at distal end 45 of tubing 42.Mechanical connector 52 in this example is a luer lock fitting that isconfigured to mate with a corresponding luer lock fitting on fluidpressurizing unit 18 (FIG. 1) so as to create a fluid tight connectionbetween the fluid pressurizing unit and fluid transfer set 40. In someapplications in accordance with this example, the fluid pressurizingunit is a syringe.

To place fluid transfer set 40 in service, an operator may insert bottlespike 50 into container 14 and secure the container to base 48 so thatthere is a connection between the container and proximal end 44 of thefluid transfer set. The operator may further engage the luer lockfitting 52 with a corresponding luer lock fitting on pressurizing unit18 so that there is a connection between the pressurizing unit anddistal end 45 of the fluid transfer set. In this manner, fluidcommunication can be established between container 14 and fluidpressurizing unit 18 using a fluid transfer set that defines twoconnection locations. Container 14, fluid transfer set 40 and, in someexamples, pressurizing unit 18 may be used repeatedly during multipleinjection procedures to transfer medical fluid from a multi-dosecontainer to a pressurizing unit.

FIG. 3 is an illustration of another example configuration of a fluidtransfer set 60 that may be used in fluid delivery system 10. Fluidtransfer set 60 is configured to fluidly connect at least one container14 (FIG. 1) to fluid pressurizing unit 18. In the illustrated example ofFIG. 3, fluid transfer set 60 is configured to connect three containersto a fluid pressurizing unit 62 that is shown as a peristaltic pump.Fluid transfer set 60 includes a first length of flexible polymerictubing 64 that extends from a proximal end 66 to a distal end 68, asecond length of flexible polymeric tubing 70 that extends from aproximal end 72 to a distal end 74, and a third length of flexiblepolymeric tubing 76 that extends from a proximal end 78 to a distal end80. The first and second lengths of tubing 64 and 70 may each fluidlyconnect a container of contrast media to pump 62. The third length oftubing 76 may fluidly connect a container of saline to pump 62.

In the example of fluid transfer set 60, proximal end 66 of first tubing64 and proximal end 72 of second tubing 70 are each connected to amechanical connector 82 that is configured to mate with a container soas to create a fluid tight connection between the container and thefluid tubing. Third tubing 76 also has a mechanical connector 84 that isconfigured to mate with a container holding saline so as to create afluid tight connection between the container and fluid tubing. At theopposite end, first tubing 64 and third tubing 76 are each connected attheir distal ends to a fluid pressurizing unit inlet connector 86 (e.g.a pump inlet connector). Fluid pressurizing unit inlet connector 86 isconfigured to mate with a fluid pressurizing unit (e.g., pump 62) so asto create a fluid tight connection between the connector and the pump.Second fluid tubing 70 is connected directly to pump 62 and, indifferent examples, may be connected upstream of the pump so that fluidfrom the tubing is pressurized within the pump or downstream of the pumpso that fluid from the tubing bypasses pressurization within the pump.

To place fluid transfer set 60 in service, an operator may connectmechanical connectors 82 to first and second tubing 64 and 70 andfurther connect mechanical connectors 82 and 84 to correspondingcontainers filled with medical fluid(s). The operator may furtherconnect fluid pressurizing inlet connector 86 to an inlet of pump 62,thereby establishing fluid communication between the first and thirdtubing 64 and 76 and pump 62. Second tubing 70 may be connected to fluidpressurizing inlet connector 86 or may have a separate mechanicalconnector that an operator separately connects to pump 62. Whenassembled, fluid communication may be established between two containersholding contrast media, one container holding saline, and pump 62. Fluidtransfer set 60 may define connections at least between mechanicalconnectors 82 and first and second tubing lines 64 and 70, a connectionbetween fluid pressurizing unit inlet connector 86 and pump 62, and aconnection between second tubing 70 and pump 62. First tubing line 64,second tubing line 70, and third tubing line 76 along with thecontainers to which the tubing is connected may be used repeatedlyduring multiple injection procedures to transfer medical fluid from thecontainers to pump 62. Pump 62 and a patient line or discharge line 30to which a discharge outlet of the pump is connected may be replaced foreach patient and/or each injection procedure.

FIG. 4 is a cross-sectional illustration of an example mechanicalconnector 100 that can be used in fluid delivery system 10 (FIG. 1) toconnect a tubing line to container 14 housing a medical fluid.Mechanical connector 100 defines a base 102 that is configured to bepositioned around rim 104 of the container 14 so that fluid does notleak out between the connector and the container. Mechanical connector100 also includes a spike 106 that is inserted into an aperture 108defined by rim 104. Spike 106 may pierce a seal that extends overaperture 108 to close and hermetically seal the container, e.g., forshipping and storage prior to use. In the illustrated example, spike 106pierces a seal that includes a septum 110 and a foil or collar 112. Whenspike 106 pierces septum 110 and foil/collar 112 to access an interiorof container 14, tubing 114 is placed in fluid communication with thecontents of the container and can receive and convey the contents, e.g.,to fluid pressurizing unit 18.

To help ensure that the various components of fluid delivery system 10(FIG. 1) do not lose their physical integrity or provide pathways thatallow contaminants to enter a sterile medical fluid during the course ofuse, fluid delivery system 10 may be tested to evaluate and validate theintegrity of the system. For example, if fluid delivery system 10 wereto be used to transfer medical fluid from container 14 to fluidpressurizing unit 18 in a non-sterile environment (e.g., in an imagingsuite), the fluid delivery system may be validated to help ensure thesystem will be safe and sterile during the course of service.

FIGS. 5A-5B, 6, and 7A-7B, are flow diagrams illustrating exampletechniques that may be performed to validate the integrity and sterilityof a medical fluid delivery system including, e.g., components of thesystem that may be used multiple times during multiple different patientinjection procedures. For ease of description, the techniques of FIGS.5-7 will generally be described with reference to fluid delivery system10 in FIG. 1. The techniques can be performed on fluid delivery systemshaving other configurations, as described herein, and it should beappreciated that the techniques are not limited to the example fluiddelivery system of FIG. 1.

In addition, in practice, the techniques of FIGS. 5A-5B, 6, and 7A-7Bcan be executed in a number of different environments. In one example,the techniques are performed in a cleanroom to help prevent externalcontaminants from entering medical fluids during testing. In anotherexample, the techniques are performed under a laminar flow air hood,again to help prevent external contaminants from entering medical fluidsduring testing. Other locations for performing the techniques are alsopossible.

With reference to FIG. 5A, the example technique includes applying oneor more pathogens (e.g., one or more viruses and/or bacteria) to one ormore components in fluid delivery system 10 (200). For example, a usermay apply the pathogen by rubbing or brushing a culture containing thepathogen on the one or more components or by immersing the components ina culture containing the pathogen. By applying the pathogen to the oneor more components, a user may determine the ability of fluid deliverysystem 10 to resist the passage of microorganisms into fluid pathwaysthat convey medical fluid from container 14 to a patient during aninjection procedure.

In some examples, the pathogen is applied at a connection betweendifferent components in fluid delivery system 10. The connection, whichis where different components are detachably joined, may provide themost likely pathway through which the pathogen could enter a medicalfluid in the system. For example, the pathogen may be applied at aconnection (e.g., all connections) between container 14 and fluidtransfer set 16 and/or a connection (e.g., all connections) betweenfluid transfer set 16 and fluid pressurizing unit 18. In differentexamples, the pathogen is applied after the components are joinedtogether to test whether external contamination of joined components canenter a medical fluid or before the components are joined together totest whether external contamination of components before joining canallow the contamination to enter the medical fluid.

When fluid transfer set 16 is configured in the example of FIG. 2, forinstance, the pathogen may be applied to mechanical connector 46 and/orcontainer 14 (e.g., a seal covering the container) before the componentsare joined together. The pathogen may be applied to external surfaces ofmechanical connector 46 and/or container 14 that would be touched by anoperator during normal use. A user may subsequently insert spike 50 ofmechanical connector 46 into container 14 to fluidly connect the fluidtransfer set to the container. Alternatively, mechanical connector 46may be mated with container 14 to define a fluid tight connectionbetween the two components and, thereafter, the pathogen applied at thejunction where the two components mate.

In addition to or in lieu of applying the pathogen to mechanicalconnector 46 and/or container 14, the pathogen can be applied tomechanical connector 52 and/or fluid pressurizing unit 18. In oneexample, the pathogen is applied to external surfaces of mechanicalconnector 52 and/or fluid pressurizing unit 18 that would be touched byan operator during normal use. For example, the pathogen may be appliedaround the external surface of a luer lock fitting and/or at an inlet ofa syringe barrel or fluid pump. A user may subsequently mate mechanicalconnector 52 with a corresponding connector on fluid pressurizing unit18 to fluidly connect the fluid transfer set to the fluid pressurizingunit.

As another example, specifically when fluid transfer set 16 isconfigured as shown in the example of FIG. 3, the pathogen may beapplied to mechanical connectors 82, 84 and/or the containers to whichthe connectors join, as described above with respect to the fluidtransfer set of FIG. 2. The pathogen may be applied to mechanicalconnectors 82, 84 and/or the containers to which the connectors joinbefore mating the connectors with the containers or after mating theconnectors with the containers. In addition to or in lieu of applyingthe pathogen to the mechanical connector and/or containers, the pathogencan be applied at one or more connections where tubing mates with pump62. For example, the pathogen may be applied on external surfaces offluid pressurizing unit inlet connector 86 and/or an inlet of pump 62 towhich the connector mates before or after the components are matedtogether.

The type and amount of pathogen applied at connection locations and/orto components within fluid delivery system 10 may vary, e.g., based onthe severity and parameters of testing. When bacteria is used as thepathogen, example bacteria that may be applied include, but are notlimited to, Staphylococcus aureus, Staphylococcus epidermidis,Pseudomanas aeruginosa, Klebsiella pneumonia, Escherichia coli, Candidaalbicans, and Aspergillus niger. In some examples, multiple types ofbacteria are applied to fluid delivery system 10, for example eithersimultaneously together or by conducting serial tests using one type ofbacteria and then another type of bacteria, to evaluate the ability offluid delivery system 10 to resist the passage of different types ofmicroorganisms. In one example, at least 100 colony formingunits/milliliter (CFU/ml) of bacteria are applied to each component orconnection location during the technique of FIG. 5A such as, e.g., atleast 500 CFU/ml, at least 1000 CFU/ml, or at least 5000 CFU/ml.Bacteria applied to fluid delivery system 10 may be in an organismdiluent, such as Mile's Test Soil or Tryptic Soy Broth.

In applications where the pathogen is applied to the components of fluiddelivery system 10 prior to assembly, the components may subsequently bedisinfected (201) and assembled (202) to place the components in fluidcommunication with one another. Disinfecting the components of fluiddelivery system 10 prior to assembly may remove surface pathogens fromthe components so that the pathogens are not deliberately introducedinto medical fluid during assembly of the components. For example, byapplying the pathogen to one or more components of fluid delivery system10 and then disinfecting the surfaces of the components, the techniqueof FIG. 5A may be used to determine whether the pathogen bypassed a sealor barrier of the components (e.g., a seal covering a medial fluidcontainer) or otherwise invaded the components such that surfacedisinfection does not remove the pathogen.

To disinfect the one or more components of fluid delivery system 10(201), a disinfectant designed to kill and/or remove the pathogen can beapplied to surfaces of the components where the pathogen was originallyapplied. An example disinfectant is an isopropyl alcohol solution (e.g.,containing greater than 60% isopropyl alcohol such as approximately 70%isopropyl alcohol), although other disinfectants can be used. Thedisinfectant can be applied to or impregnated in a cloth that is thenwiped over the surfaces of the components. In some examples, the clothis wiped over a surface of a component so that the cloth is in contactwith the component for a period of time greater than 5 seconds such as,e.g., a period greater than 20 seconds, a period greater than 30seconds, or a period of time ranging from approximately 25 seconds andapproximately 30 seconds.

When fluid transfer set 16 is configured in the example of FIG. 2, forinstance, mechanical connector 46 and/or container 14 (e.g., a sealcovering the container) may be disinfected by wiping a cloth containinga disinfectant over the surfaces of the mechanical connector and/orcontainer to which the pathogen was applied. As another example, whenfluid transfer set 16 is configured as shown in the example of FIG. 3,mechanical connectors 82, 84 and/or the containers to which theconnectors join may be disinfected by wiping a cloth containing adisinfectant over the surfaces of the mechanical connectors and/orcontainers to which the pathogen was applied.

In addition to or in lieu of disinfecting the one or more components offluid delivery system 10 (201) after applying the pathogen (200) asdescribed above, the one or more components of fluid delivery system 10may be disinfected prior to applying the pathogen (200). For example, adisinfectant designed to kill and/or remove the pathogen can be appliedto surfaces of the components where the pathogen is to be applied.Disinfecting the surfaces of the components where the pathogen is to beapplied can clean and sterilize the components. This can help ensurethat any pathogenic ingress subsequently identified in fluid deliverysystem 10 is attributable to the controlled application of the pathogenaccording to the technique of FIG. 5A and not external sources. Whendisinfected prior to applying the pathogen, the one or more componentsof fluid delivery system 10 can be disinfected, e.g., using thetechniques described above for disinfecting the one or more componentsafter application of the pathogen.

Independent of whether the one or more components of fluid deliverysystem 10 are disinfected, the components may be assembled (202) toplace the components in fluid communication with one another. When theone or more components are disinfected prior to assembly (201), thecomponents may first be allowed to dry for a period of time prior toassembly such as a period of greater than 10 seconds, greater than 30seconds, or greater than approximately 1 minute. The components of fluiddelivery system 10 can be assembled in accordance with fluid deliverysystem use instructions. To assemble fluid transfer set 16 (FIG. 1) influid delivery system 10, for example, an operator can mate a mechanicalconnector positioned at a proximal end 34 of the fluid transfer set withcontainer 14. As the mechanical connector is mated with container 14,the connector may pierce a seal on the container, allowing fluid to flowfrom the container into the fluid transfer set. The operator may alsomate a mechanical connector at distal end 36 of the fluid transfer setwith fluid pressurizing unit 18 so as to place the fluid transfer set influid communication with the pressurizing unit.

With further reference to FIG. 5A, the example technique also includesdrawing fluid from container 14 through fluid transfer set 16 and intofluid pressurizing unit 18 (203). Subsequent to applying the pathogen tothe one or more components of fluid delivery system 10 (200) anddisinfecting (201) and assembling (202) the components, fluid is drawnthrough the system to evaluate if the pathogen will enter the fluidduring typical filling and injection operations. Fluid may be drawn fromcontainer 14 through fluid transfer set 16 and into fluid pressurizingunit 18 immediately after applying the pathogen or after the pathogenhas been applied for a certain amount of time. For example, fluid may bedrawn through fluid delivery system 10 after the pathogen has beenapplied and allowed to reside in or on the components of the system fora period of at least 1 hour such as, e.g., a period greater than orequal to 4 hours, a period greater than or equal to 8 hours, or a periodgreater than or equal to 10 hours. Of course, the fluid deliverycomponents may first be disinfected (201), allowed to dry, and assembledafter the pathogen is allowed to reside on the components for any of theforegoing periods of time.

The technique of FIG. 5A also includes extracting a sample of medicalfluid from within fluid delivery system 10 (204). The fluid sample maybe extracted by operating fluid pressurizing unit 18 to dischargepressurized medical fluid through discharge outlet 28. The sample may becollected at the discharge outlet, e.g., from discharge line 30.Additionally or alternatively, a fluid sample may be extracted bydisconnecting detachably connected components in fluid delivery system10 and extracting a sample of fluid from within the components. Forexample, fluid transfer set 16 may be detached from container 14 and/orfluid pressurizing unit 18 and a sample of fluid taken from withincontainer 14, from within the fluid transfer set, and/or from withinfluid pressurizing unit 18.

Independent of the specific technique used to extract a sample fromfluid delivery system 10 (204), the sample is subsequently analyzed(206) to determine a concentration level of the pathogen applied to thefluid delivery system in the fluid sample. The determined pathogen levelmay be compared to a concentration level of the pathogen in the medicalfluid within container 14 before the container was connected to fluiddelivery system 10 and challenged with the pathogen. For example, aconcentration level of the pathogen in the medical fluid withincontainer 14 before the container was connected to fluid delivery system10 and challenged with the pathogen may be zero. If the extracted sampleis determined to also have a pathogen concentration level of zero, fluiddelivery system 10 may be validated as successfully resisting thepassage of microorganisms into fluid pathways. Different tolerancelevels may be established depending on the requirements of a particularapplication.

FIG. 5B is a flow diagram of an example implementation of the techniqueof FIG. 5A, where like process steps described above with respect toFIG. 5A are designated with like reference numerals. As shown in FIG.5B, the example technique includes applying one or more pathogens (e.g.,one or more bacteria and/or viruses) to the one or more components offluid delivery system 10 (200), such as a portion of a component orportions of components that join together to form a connection.Subsequent to applying the pathogen to the one or more components offluid delivery system 10 (200), the components may be disinfected (201)and assembled (202) to place the components in fluid communication withone another.

Once the pathogen challenged components are assembled, fluid is drawnthrough the system to evaluate if the pathogen will enter the fluidduring typical filling and injection operations (203). Fluid can bedrawn from container 14 through fluid transfer set 16 and into fluidpressurizing unit 18 by operating (e.g., activating) the fluidpressurizing unit. In the technique of FIG. 5B, fluid pressurizing unit18 is operated multiple times (300) to discharge multiple portions offluid from the fluid pressurizing unit 18 via discharge outlet 28. Forexample, fluid pressurizing unit 18 may be activated a first time todraw fluid from container 14 through fluid transfer set 16 and thendischarge a first portion of pressurized fluid out through dischargeoutlet 28. After dispensing a suitable volume of fluid, fluidpressurizing unit 18 may cease operation so that no fluid is beingdispensed from discharge outlet 28. Fluid pressurizing unit 18 maysubsequently be activated a second time to draw additional fluid fromcontainer 14 through fluid transfer set 16 and discharge a secondportion of pressurized fluid out through discharge outlet 28. Afterdischarging a suitable volume of fluid, fluid pressurizing unit 18 mayagain cease operation so that no fluid is being dispensed from dischargeoutlet 28. The process of activating fluid pressurizing unit 18 andceasing operation of the unit can be repeated any additional number oftimes, such as one, two, three, or more times, e.g., to convey a certainvolume of fluid and/or generate a certain number of discharged fluidportions.

Operating fluid pressurizing unit 18 multiple times to generate multipleportions of fluid (300) may be useful to simulate real-world operationof fluid delivery system 10 when the system is used to inject multiplepatients with fluid from container 14 during multiple sequential patientinjection procedures. During each patent injection procedure, fluidpressurizing unit 18 is operated to draw fluid from container 14 anddischarge the fluid under pressure into catheter 32 connected to apatient. After each patient injection procedure, fluid pressurizing unit18 ceases operation and, in some examples, is replaced with a new,sterile fluid pressurizing unit. The fluid pressurizing unit can then beoperated during a subsequent injection procedure to inject a new patientwith pressurized medical fluid. The process can be repeated foradditional patient injection procedures.

By operating fluid pressurizing unit 18 multiple times to dischargemultiple portions of fluid (300) during validation testing, fluiddelivery system 10 can be evaluated for resistance to pathogenic ingressduring a normal course of operation. Fluid pressurizing unit 18 can beoperated any desired number of times to generate any desired number ofportions or volumes of fluid during the performance of the method ofFIG. 5B. In some examples, fluid pressurizing unit 18 is operated atleast twice (e.g., three, four, or more times) to provide at least twoportions of fluid (e.g., three, four, or more portions of fluid) thatare discharged from the fluid pressurizing unit during operation. Fluidpressurizing unit 18 may cease operation for a given period of timebetween each cycle in which the unit is operated to discharge fluid. Forexample, the fluid pressurizing unit 18 may remain inactive for a periodof at least 5 minutes between each cycle of operation, such as a periodof at least 20 minutes, a period of at least one hour, a period of atleast 2 hours, a period ranging from 5 minutes to 5 hours, or a periodranging from 10 minutes to 2 hours. As described in greater detailbelow, a fluid sample can be extracted from one more of the portions offluid discharged from fluid pressurizing unit 18 for subsequent analysis(204).

The volume of fluid discharged from fluid pressurizing unit 18 duringthe performance of the technique of FIG. 5B can vary, e.g., depending onthe capacity of container 14, the discharge rate of the fluidpressurizing unit, and the amount of time the fluid pressurizing unit isoperated during each cycle. Moreover, when attempting to simulatereal-world operation of fluid delivery system 10, the fluid deliverysystem can, in different operating environments, be operated in a lowvolume throughput scenario in which only a few patients would beinjected during a day of operation or a high volume throughput scenarioin which many patients would be injected during a day of operation.

In a comparatively low volume throughput environment, fluid deliverysystem 10 may be connected to a single container 14 (e.g., contrast,saline) or single set of containers (e.g., a container of contrast and acontainer of saline) that are used throughout a single day withoutreplacement. Accordingly, to simulate comparatively low volumeoperation, fluid pressurizing unit 18 may be operated so that eachportion of fluid discharged from the fluid pressurizing unit is drawnfrom the same container or set of containers, e.g., without replacing acontainer between operating cycles of the fluid pressurizing unit. Insuch an application, each sample of fluid extracted from fluid deliverysystem 10 (204) and analyzed for the pathogen (206) may originate fromthe same container or set of containers. In some cases, each sample offluid may be obtained from a discharged portion of fluid withoutdisassembling fluid system 10 (e.g., disconnecting container 14, fluidtransfer set 16, and/or fluid pressurizing unit 18), which may otherwiseintroduce contamination into the system.

As one example of a low volume throughput simulation, specifically whenfluid transfer set 16 is configured as shown in the example of FIG. 3,connector 82 may be attached to a container of contrast sized to providemultiple doses of fluid to multiple different patients (e.g., 500milliliters) and connector 84 may be attached to a container of salinesized to provide multiple doses of fluid to multiple different patients(e.g., 500 milliliters). Fluid pressurizing unit 18 can then beperiodically operated to dispense a portion of fluid that is drawn fromthe container of contrast and/or the container of saline. For example,to simulate a patient dose, fluid pressurizing unit 18 may be operatedto dispense 100 milliliters of contrast followed by 30 milliliters ofsaline, thereby dispensing a first portion of fluid that is 130milliliters. Fluid pressurizing unit 18 may be operated to subsequentlydispense additional portions of fluid that are each composed of 100milliliters of contrast followed by 30 milliliters of saline. Forexample, fluid pressurizing unit 18 may be operated to dispense a firstportion of fluid upon initial assembly of fluid delivery system 10, asecond portion of fluid four hours after assembly, a third portion tenhours after assembly, and a fourth portion twelve and a half hours afterassembly. The container of contrast and container of saline in such anexample would have a capacity sufficient to allow all four portions offluid to be drawn from the same set of containers.

In contrast to a low volume throughput environment, in a comparativelyhigh volume throughput environment, the container 14 (e.g., contrast,saline) or a set of containers (e.g., a container of contrast and acontainer of saline) connected to fluid delivery system 10 may bereplaced throughout a day of operation as the contents of the containersare exhausted. Accordingly, to simulate comparatively high volumeoperation, fluid pressurizing unit 18 may be operated a sufficientnumber of times to empty the container or set of containers. Uponemptying the containers, the container or set of containers to whichfluid pressurizing unit 18 is fluidly connected may be replaced with areplacement container or set of containers filled with medical fluid(302). After replacement, fluid pressurizing unit 18 may again beoperated to dispense portions of fluid from the replacement containers.

As one example of a high volume throughput simulation, specifically whenfluid transfer set 16 is configured as shown in the example of FIG. 3,connector 82 may be attached to a container of contrast sized to providea dose of fluid to multiple different patients (e.g., 200 milliliters)and connector 84 may be attached to a container of saline sized toprovide a dose of fluid to multiple different patients (e.g., 500milliliters). Fluid pressurizing unit 18 can then be periodicallyoperated to dispense a portion of fluid that is drawn from the containerof contrast and/or the container of saline. For example, to simulate apatient dose, fluid pressurizing unit 18 may be operated to dispense 100milliliters of contrast followed by 30 milliliters of saline, therebydispensing a first portion of fluid that is 130 milliliters. Fluidpressurizing unit 18 may be operated additional times at a frequencysufficient to consume multiple containers of contrast and/or multiplecontainers of saline over a given period of time. For example, fluidpressurizing unit 18 may be operated at a frequency sufficient toconsume twenty containers of contrast and four containers of saline overa twelve and a half hour period by dispensing discrete 130 milliliterportions of contrast and saline. The containers of contrast and salinemay be replaced with full replacement containers as the in-servicecontainers connected to fluid delivery system 10 become exhausted. Insuch an application, different samples of fluid extracted from fluiddelivery system 10 (204) and analyzed for the pathogen (206) mayoriginate from different containers or different sets of containers.Such an application may be useful to evaluate the tendency of thepathogen to invade fluid system 10 during the course of high volumeoperation when medical fluid containers are being replaced multipletimes per day.

Independent of whether fluid delivery system 10 is operated to simulatelow volume throughput, a high volume throughput, or both low and highvolume throughputs, the technique of FIG. 5B includes applying thepathogen to one or more components in fluid delivery system 10 (200).For example, when fluid transfer set 16 is configured as shown in theexample of FIG. 3, the pathogen may be applied to connector 82 (e.g., aconnection between a container such as container 14 and connector 82), aproximal end 66 of the first length of tubing 64 and connector 82 (e.g.,a connection between the components), at connector 84 (e.g., aconnection between a container and connector 84), and/or at a connectionbetween fluid pressurizing unit inlet connector 86 and pump 62. Afterapplying the pathogen to the components (200), the components may bedisinfected (201) and assembled (202), as described with respect to FIG.5A.

In instances where a fluid container or set of fluid containers isreplaced during performance of the method of FIG. 5B (302), the pathogenmay or may not be reapplied to some or all of the connection locationswhere the pathogen was applied during initial assembly of fluid deliverysystem 10. Reapplying the pathogen may be useful to evaluate thetendency of the pathogen to invade fluid system 10 during the course ofhigh volume operation when medical fluid containers are being replacedmultiple times per day. When the pathogen is reapplied, the componentsmay again be disinfected (201) and then reassembled (202).

After or while operating fluid pressurizing unit 18 multiple times overa given period to draw fluid through fluid delivery system 10 anddispense multiple portions of fluid from the unit (203), a plurality offluid samples of fluid are extracted for analysis (204). Each sample offluid may be from a different portion of fluid dispensed during adifferent cycle of operation of fluid pressurizing unit 18. In oneexample, a sample of fluid is obtained from each portion of fluiddischarged from fluid pressurizing unit 18. In another example, a sampleof fluid is obtained from some but not all portions of fluid dischargedfrom fluid pressurizing unit 18. For example, an operator may extract asample from a first portion of fluid dispensed from fluid pressurizingunit 18 upon initial assembly of fluid delivery system 10 and/or asample from a last portion of fluid dispensed from the fluidpressurizing unit during a final operation. An operator may extractadditional or different samples. For instance, in addition to extractinga sample from a first portion of fluid and a sample from a last portionof fluid, the operator may extract one or more (e.g., two, three, ormore) additional samples from portions of fluid dispensed between thefirst portion of fluid and the last portion of fluid.

The technique of FIG. 5B also includes analyzing the plurality ofsamples (206) to determine a concentration level of the pathogen appliedto the fluid delivery system in the plurality of fluid samples. In someexamples, each of the plurality of samples obtained from the multipleportions of fluid are combined together to form a pooled sample. In suchapplications, the pooled sample may be analyzed to determine aconcentration level of the pathogen in the pooled sample. In otherexamples, each of the plurality of samples is separately analyzed todetermine a concentration level of the pathogen in each respectivesample. In either case, if a sample is determined to have a lowconcentration level (e.g., zero) for the pathogen or combination ofpathogens originally applied to fluid delivery system 10, the fluiddelivery system may be validated as successfully resisting the passageof microorganisms into fluid pathways.

In some examples, the technique of FIG. 5B is repeated under both highvolume throughput conditions and low volume throughput conditions tovalidate fluid delivery system 10, or a component thereof. For example,the technique may be performed once under high throughput conditions inwhich multiple containers of contrast and/or saline are consumed togenerate samples of discharged fluid that originated from differentcontainers or sets of containers. The samples obtained during highthroughput testing can be pooled together and analyzed to determine aconcentration level of the pathogen in the pooled sample. In addition,the technique may be performed again under low throughput conditions. Inlow throughput conditions, only a single container or set of containersof contrast and/or saline may be consumed to generate samples ofdischarged fluid that all originated from the same container or set ofcontainers. The samples obtained during low throughput testing can alsobe pooled together and analyzed to determine a concentration level ofthe pathogen in the pooled sample. In some applications, fluid deliverysystem 10 may be validated as successfully resisting the passage ofmicroorganisms into fluid pathways if both the pooled sample from highthroughput testing and the pooled sample from low throughput testing aredetermined to have a sufficiently low concentration level (e.g., zero)of the pathogen.

FIG. 6 is a flow diagram illustrating another example technique that maybe used to validate the integrity and sterility of a medical fluiddelivery system. The components of the medical fluid delivery system maybe assembled together (e.g., so that a fluid transfer set is in fluidcommunication with both a container of medical fluid and a fluidpressurizing unit). Once assembled, the example technique includesdrawing fluid from container 14 through fluid transfer set 16 and intofluid pressurizing unit 18 so as to fill fluid holding areas in fluiddelivery system 10 with medical fluid (208). Although fluid deliverysystem 10 can be filled with any medical fluid as described herein, insome examples, the medical fluid is contrast media. By filling fluiddelivery system 10 with contrast media, a user may determine the abilityof the components of fluid delivery system 10 to resist chemicaldegradation, including multi-use components that may be used during thecourse of multiple patient injections.

Subsequent to filling fluid transfer set 16 and fluid pressurizing unit18 with medical fluid, the medical fluid is held in the fluid transferset and fluid pressurizing unit for a period of time (210). Thecomponents of fluid delivery system 10 may be held full of fluid for aperiod of time so that the fluid contacts interior surfaces of thecomponents that would normally be fluid-wet during filling and/ordischarge of powered fluid injector 12. In some examples, the fluid isstatic (e.g., not moving) within fluid delivery system 10 as thecomponents of the system are held full of fluid. In other examples, thefluid may be moving through fluid delivery system 10 during the periodof time in which the components are held full of fluid.

The components of fluid delivery system 10 can be held full of fluid forany period of time suitable for evaluating the ability of the componentsto resist chemical degradation (210). In applications where a multi-usecomponent is intended to remain in service during the course of multiplefluid injections, the component may be exposed to fluid continuously orintermittently for an extended period of time such as an entire shift orentire day. Accordingly, in some examples, the components of fluiddelivery system 10 may be held full of fluid for a period of timegreater than or equal to 1 hour such as, e.g., a period of time greaterthan or equal to 2 hours, a period of time greater than or equal to 4hours, or a period of time greater than or equal to 8 hours. Forinstance, the components of fluid delivery system 10 may be held full offluid for a period of time ranging from approximately 1 hour toapproximately 48 hours such as, e.g., from approximately 4 hours toapproximately 24 hours, or approximately 8 hours to approximately 16hours.

After holding the components of fluid delivery system 10 (e.g., fluidtransfer set 16 and fluid pressurizing unit 18) full of medical fluid, asample of the medical fluid can be extracted for analysis (212). Thefluid sample may be extracted by operating fluid pressurizing unit 18 todischarge pressurized medical fluid through discharge outlet 28. Thesample may be collected at the discharge outlet. Additionally oralternatively, a fluid sample may be extracted by disconnectingdetachably connected components in fluid delivery system 10 andextracting a sample of fluid from within the components. For example,fluid transfer set 16 may be detached from container 14 and/or fluidpressurizing unit 18 and a sample of fluid taken from within container14, from within the fluid transfer set, and/or from within fluidpressurizing unit 18.

The extracted sample is analyzed to determine if any components of thefluid delivery system have chemically degraded with exposure to themedical fluid (214). The fluid may be analyzed to determine if amaterial(s) used to fabricate components of fluid delivery system 10(e.g., a material used to fabricate fluid transfer set 16 and/or fluidpressurizing unit 18) have entered the medical fluid held within thecomponents. In one example, the fluid is analyzed to determine if thereare any particles in the fluid greater than a certain size such as,e.g., greater than 10 micrometers, greater than 100 micrometers, orgreater than 1 millimeter. Such particles may be pieces of a componentof fluid delivery system 10 that have detached from the component. Ifthe extracted sample is determined to not have particles greater than acertain size or not have a certain number of particles greater than thecertain size, fluid delivery system 10 may be validated as beingchemically compatible and maintaining chemical integrity with themedical fluid (e.g., the class of medical fluids).

In addition to or in lieu of analyzing the extracted sample forparticles, the extracted sample may be analyzed to determine if achemical present in the material(s) used to fabricate components offluid delivery system 10 (e.g., a material used to fabricate fluidtransfer set 16 and/or fluid pressurizing unit 18) has leached into themedical fluid held within the components. As examples, the extractedfluid sample may be analyzed to determine if one or more of thefollowing chemical compounds are present in the fluid: cyclohexanone,2-ethyl-1-hexanol, di(2-ethylhexyl)phthalate (DEHP), epoxidized soybeanoil, tris (nonylphenyl) phosphate (TNPP), stearic acid, zinc or otherheavy metals. The extracted sample may be analyzed using gaschromatography, high-performance liquid chromatography, inductivelycoupled plasma mass spectrometry (ICP-MS), or any other suitabletechniques. A determined concentration level of the chemical compound(s)may be compared to a concentration level in the medical fluid withincontainer 14 before the container was connected to fluid delivery system10 and exposed to the components in the system. For example, aconcentration level of the chemical compound(s) in the medical fluidwithin container 14 before the container was connected to fluid deliverysystem 10 and drawn through the system may be zero. If the extractedsample is determined to also have a concentration level of zero for thechemical compound(s), fluid delivery system 10 may be validated as beingchemically compatible and not leaching chemical compound(s) into themedical fluid. Different tolerance levels may be established dependingon the requirements of a particular application.

FIG. 7A is a flow diagram illustrating another example technique thatmay be used to validate the integrity and sterility of a medical fluiddelivery system. The technique may be used to confirm thatcross-contamination of fluids between patients will not occur when usingfluid delivery system 10 by having fluid from a patient-specific tube(e.g., downstream of fluid pressurizing unit 18) mix with fluid in amulti-use tube (e.g., upstream of fluid pressurizing unit 18). Thecomponents of the medical fluid delivery system may be assembledtogether (e.g., so that a fluid transfer set is in fluid communicationwith both a container of medical fluid and a fluid pressurizing unit).Once assembled, the example technique includes drawing fluid fromcontainer 14 through fluid transfer set 16 and into fluid pressurizingunit 18 so as to fill fluid holding areas in fluid delivery system 10with medical fluid (216). By drawing medical fluid from container 14through fluid transfer set 16 and into fluid pressurizing unit 18, thefluid holding regions of fluid delivery system 10 upstream of fluidpressurizing unit 18 may be filled with medical fluid.

In addition, in the technique of FIG. 7A, discharge outlet 28 of fluiddelivery system 10 is placed in fluid communication with a fluidreservoir containing a tracking fluid (218). The fluid reservoir may bea bottle, bag, pouch, syringe, or tube filled with fluid, or any othersuitable reservoir. The tracking fluid may contain a tracking agent notpresent in the medical fluid in container 14. The tracking agent may betracked to determine if fluid downstream of discharge outlet 28 migratesinto fluid pressurizing unit 18 and/or upstream of fluid pressurizingunit 18. For example, the tracking agent may simulate the movement ofblood borne pathogens, were discharge outlet 28 in fluid communicationwith a catheter inserted into a patient. Example tracking agents mayinclude, but are not limited to, bacteria, viruses, dyes, radioactiveisotopes, and electro-magnetic markers.

To simulate cross-contamination conditions, the fluid reservoircontaining the tracking agent is blocked so that fluid pressurizing unit18 cannot draw medical fluid from container 14 and inject the fluid intothe fluid reservoir containing the tracking agent. Configuring the fluidreservoir containing the tracking agent as a closed reservoir maysimulate conditions in which a patient's catheter 32 is blocked andfluid pressurizing unit 18 is attempting to inject fluid into a blockedor partially occluded catheter. Were the fluid reservoir containing thetracking agent not closed, fluid pressurizing unit 18 could draw fluidfrom container 14 and inject the fluid into the reservoir, preventingthe tracking agent from migrating upstream in fluid delivery system 10.By contrast, when fluid pressurizing unit 18 discharges medical fluidthrough discharge outlet 28 against a closed reservoir of trackingfluid, a generally static interface may be created where dischargedmedical fluid meets tracking fluid, potentially resulting in mixing andupstream migration of the tracking fluid into the upstream medicalfluid.

Accordingly, after placing discharge outlet 28 of fluid delivery system10 in fluid communication with a fluid reservoir containing a trackingfluid (218), fluid pressurizing unit 18 is operated to try and dischargepressurized medical fluid into the tracking fluid (220). For example,when fluid pressurizing unit is a pump, the pump may operatecontinuously for a period of time even though the pump may notnecessarily be conveying fluid because the fluid path downstream of thepump is blocked or restricted. Fluid pressurizing unit 18 may operatefor any suitable period such as, e.g., greater than 1 minute, greaterthan 15 minutes, greater than 30 minutes, or greater than 1 hour.

After operating fluid pressurizing unit 18 for a period of time (220), asample of medical fluid is extracted from fluid delivery system 10 foranalysis (222). The fluid sample may be extracted by disconnectingdetachably connected components in fluid delivery system 10 andextracting a sample of fluid from within the components. For example,fluid transfer set 16 may be detached from container 14 and/or fluidpressurizing unit 18 and a sample of fluid taken from within container14, from within the fluid transfer set, and/or from within fluidpressurizing unit 18.

The extracted sample is analyzed to determine a concentration level ofthe tracking agent in the sample of medical fluid (224). The determinedconcentration level may be compared to a concentration level of thetracking agent in the medical fluid within container 14 before thecontainer was connected to fluid delivery system 10. For example, aconcentration level of the tracking agent in the medical fluid withincontainer 14 and/or transfer set 16 before the container was connectedto fluid delivery system 10 may be zero. If the extracted sample isdetermined to also have a concentration level of zero, fluid deliverysystem 10 may be validated as successfully preventingcross-contamination of fluid between a patient-specific fluid line and amulti-use fluid line. Different tolerance levels may also be establisheddepending on the requirements of a particular application.

FIG. 7B is a flow diagram illustrating another example technique thatmay be used to confirm that cross-contamination of fluids betweenpatients will not occur when using fluid delivery system 10, where likeprocess steps described above with respect to FIG. 7A are designatedwith like reference numerals. In the technique of FIG. 7B, thecomponents of the medical fluid delivery system may be assembledtogether (e.g., so that fluid transfer set 16 is in fluid communicationwith both container 14 and fluid pressurizing unit 18). Once assembled,the example technique includes filling fluid transfer set 16 and fluidpressurizing unit 18 with medical fluid (310). The components can befilled with fluid by activating fluid pressurizing unit 18 to draw fluidfrom container 14 through fluid transfer set 16 and into the fluidpressurizing unit. This can prime fluid pressurizing unit 18 and/or fillfluid holding areas in fluid delivery system 10 with medical fluid, thusproviding filled fluid pathway(s) to evaluate whether a tracking agentwill travel through the pathways, potentially indicating a risk ofcross-contamination. In some examples, fluid transfer set 16 and fluidpressurizing unit 18 are filled with a comparatively low viscositymedical fluid, such as saline, which may be more prone to permit flow ofa tracking agent than a comparatively higher viscosity fluid, such ascontrast.

In addition, in the technique of FIG. 7B, a discharge line (e.g.,discharge line 30 in FIG. 3) connected to discharge outlet 28 of fluidpressurizing unit 18 is filled with a tracking agent (312). The trackingagent may be a tracking fluid containing a tracking agent and, indifferent examples as described above with respect to FIG. 7A, can be abacteria, virus, dye, radioactive isotope, and/or electro-magneticmarker. The discharge line may be filled by introducing the trackingagent through a distal outlet of the discharge line (e.g., oppositefluid pressurizing unit 18) and allowing the tracking agent to flow downthe discharge line toward the fluid pressurizing unit. Upon initiallyfilling the discharge line with tracking agent, the tracking agent maybe positioned between discharge outlet 28 of fluid pressurizing unit 18and a distal end of discharge line 30 extending away from dischargeoutlet 28.

When filling a discharge line with tracking agent (312), the trackingagent can be introduced into the discharge line until it is positionedany suitable distance from fluid pressurizing unit 18. In general, thedistance between the tracking agent in the discharge line and the fluidpressurizing unit can be controlled by controlling the amount of medicalfluid in the discharge line before introduction of the tracking agent.For example, if fluid pressurizing unit 18 was primed with medical fluidand the discharge line was filled with a column of medical fluidextending approximately 10 centimeters away from the fluid pressurizingunit, the tracking agent may initially be positioned approximately 10centimeters away from the fluid pressurizing unit, when introduced intothe discharge line. In such an example, the column medical fluid thatdoes not contain tracking agent may function to initially separate thetracking agent from the fluid pressurizing unit.

In some examples, fluid pressurizing unit 18 provides a fluid sealadjacent discharge outlet 28 and the discharge line is filled withtracking agent until the tracking agent is positioned adjacent the fluidseal. FIGS. 8A and 8B are perspective drawings of an example peristalticpump 400 that has a fluid seal and may be used as fluid pressurizingunit 18. FIG. 8A illustrates peristaltic pump 400 outside of andinsertable into a pump housing 402, while FIG. 8B illustrates theperistaltic pump inserted into the pump housing.

As shown in the examples of FIGS. 8A and 8B, peristaltic pump 400 has aplurality of rollers 404 that are configured to squeeze (e.g., compress)a compressible tube 406. For example, when peristaltic pump 400 isinserted into pump housing 402 as illustrated in FIG. 8B, rollers 404may push radially outwards to compress compressible tube 406 betweeneach of the rollers and an opposite wall surface of the pump. Rotationof the plurality of rollers 404 pressurizes and moves medical fluidthrough the tube. In addition, locations where each of the plurality ofrollers 404 impinges upon the tube may define a fluid seal, such asfluid seal 408. Fluid seal 408 can be a location where thecross-sectional flow area of compressible tube 406 is minimized comparedto other areas of the tube and/or completely closed due to thecompressive action of the rollers.

Filling a fluid pressurizing unit, such as peristaltic pump 400, withtracking agent so the tracking agent is positioned adjacent to fluidseal 408 may be useful to simulate a worst case cross-contaminationscenario in which a simulated contaminant (tracking agent) is bestpositioned to cross from a single-patient discharge line and/orsingle-patient fluid pressurizing unit back into a multi-patient fluidtransfer set. FIG. 9 is a perspective drawing of peristaltic pump 400illustrating a discharge line 410 filled with tracking agent. Thedischarge line is filled with tracking agent so the tracking agent ispositioned adjacent to fluid seal 408. In particular, in the illustratedexample, the tracking agent impinges on fluid seal 408. When soconfigured, tracking agent may extend into a region of compressible tube406 where the cross-sectional flow area of the compressible tube isminimized compared to other areas of the tube and/or completely closeddue to the compressive action of the rollers pressing on the tube.

With further reference to FIG. 7B, the example technique also includesestablishing a positive pressure that biases the tracking agent in thedischarge line toward the fluid pressurizing unit (314). To simulatecross-contamination conditions, a pressure may be applied to thetracking agent in the discharge line that attempts to force the trackingagent back through fluid pressurizing unit 18 and into fluid transferset 16. The ability of fluid pressurizing unit 18 to resist migration oftracking agent back into fluid transfer set 16 may indicatecross-contamination resistance capabilities of the system.

Any suitable technique can be used to establish a positive pressure thatacts on the tracking agent in the discharge line. In one example, apositive pressure source (e.g., a pressurized liquid or gas) isconnected to a distal end of the discharge line, thereby establishing apositive pressure that biases fluid in the discharge line toward fluidpressurizing unit 18. In another example, the discharge line is orientedvertically with a distal end of the line open to ambient atmosphere. Insuch an example, a fluid head pressure provided by the weight of thefluid in the discharge line and gravity acting on the fluid can providepositive pressure that biases the tracking agent toward fluidpressurizing unit 18. For example, peristaltic pump 400 is illustratedin FIG. 9 with discharge line 410 extending vertically upward withrespect to ground to provide a positive pressure that biases thetracking agent toward the pump.

Independent of the specific technique used to establish a positivepressure, any suitable magnitude of pressure may act on the trackingagent to bias the tracking agent back toward the fluid pressurizingunit. In some examples, the tracking agent is biased with a positivepressure greater than 0.05 pounds per square inch gauge (psig), such asgreater than 0.1 psig, greater than 0.25 psig, greater than 0.5 psig, orgreater than 1 psig. For example, the positive pressure acting on thetracking agent at the proximal end of the discharge tube immediatelyadjacent fluid pressurizing unit 18 may range from 0.05 psig to 5 psig,such as from 0.1 psig to 2 psig, or from 0.25 psig to 1 psig. In oneexample, the pressure is greater than or equal to an average peripheralvenous pressure of a human, which is typically reported as approximately0.3 pounds per square inch. Fluid pressurizing unit 18 will typicallynot be operating while the positive pressure is acting on the trackingagent.

The technique of FIG. 7B also includes extracting a sample of medicalfluid from fluid delivery system 10 (222) and analyzing the sample todetermine a concentration level of the tracking agent in the sample(224), as discussed above with respect to FIG. 7A. Medical fluid may beextracted from fluid delivery system 10 (222) after the establishedpositive pressure (314) is allowed to act on the tracking agent for agiven period of time. In general, the longer the tracking agent is heldunder pressure and biased against fluid pressurizing unit 18, the morelikely the tracking agent is to bypass the pressurizing unit and entermedical fluid in fluid transfer set 16. In different examples, thetracking agent is held under positive pressure for a period of at least5 minutes, such as at least 15 minutes, at least 30 minutes, at least 1hour, at least 8 hours, or at least 1 day. For example, the trackingagent may be held with a positive pressure biasing the agent towardfluid pressurizing unit 18 for a period ranging from 5 minutes to 4hours, such as a period ranging from 30 minutes to 2 hours.

While the example techniques of FIGS. 5A, 5B, 6, 7A, and 7B have beendescribed as discrete techniques for validating the integrity andsterility of a medical fluid delivery system, it should be appreciatedthat any two of the techniques or all three of the techniques may beperformed on a single fluid delivery system to validate differentaspects of the system.

The following examples may provide additional details about validationtechniques and validated components in accordance with this disclosure.

EXAMPLES Example 1 Chemical Compatibility

A chemical compatibility study was performed to verify the chemicalcompatibility of the materials composing a Bracco transfer set [part no.100115] similar to that shown in FIG. 2 with Isovue-370 contrast mediaas well as to check for the presence of sub-visible and visibleparticulates and potential leachable compounds in Isovue-370, which wassubjected to contact with the transfer set during simulated use inaccordance with the validation testing. The Bracco transfer set wasconfigured as a disposable component intended to be used to fillinjector syringes, such as injector syringes of the Bracco Empower CTA®and Medrad Stellant® injectors, with Isovue-370 contrast media frommulti-dose, multi-patient containers.

To perform the chemical compatibility testing, a container closure of a500 mL bottle of Isovue-370 was pierced with the Bracco transfer set andan injector was used to draw samples from the bottle through thetransfer set into sterile, single use only injector syringe. Using a newsyringe each time, 100 mL samples were dispensed at 0, 4, 10 and 14hours by connecting the syringe to a tube and performing an injection of100 mL into a chemically clean container. Each sample was subsequentlyanalyzed along with a sample of the remaining contrast in the bottle atthe end of the 14 hour testing protocol.

Each sample was evaluated to determine if any sub-visible or visibleparticles of material were released into the fluid. In addition, eachsample was evaluated to determine if the following potentially leachablecompounds leached into the fluid: di(2-ethylhexyl) phthalate (DEHP) andOctadecyl 3,5-Di-(tert)-butyl-4-hydroxyhydrocinnamate (Irganox 1076).The results of the particle analysis are provided in Table 1 below andthe results of the leachable compounds analysis is provided in Table 2below.

TABLE 1 Injector Empower CTA ® Medrad Stellant ® ParticlesVisible >10μ >25μ Visible >10μ >25μ Spec. None <25 particles <3particles per None <25 particles <3 particles per per ml ml per ml mlTime point  0 hours None 10.13 0.27 None 6.53 0.40  4 hours None 8.270.93 None 3.60 1.07 10 hours None 13.33 0.53 None 12.40 0.53 14 hoursNone 16.80 0.40 None 2.80 0.40 Remaining None 9.33 0.13 None 15.47 1.73Contents of the Bottle at 14 Hrs.

TABLE 2 Injector Empower Medrad CTA ® Stellant ® Controls IrganoxIrganox Irganox DEHP 1076 DEHP 1076 DEHP 1076 Time point (μg/mL) (μg/mL)(μg/mL) (μg/mL) (μg/mL) (μg/mL)  0 hours <1.0 <2.5 <1.0 <2.5 <1.0 <2.5 4 hours <1.0 <2.5 <1.0 <2.5 <1.0 <2.5 14 hours <1.0 <2.5 <1.0 <2.5 <1.0<2.5 Remaining <1.0 <2.5 <1.0 <2.5 <1.0 <2.5 Contents of the Bottle at14 Hrs.

The results demonstrated that the chemical integrity of the Braccotransfer set was maintained when Isovue 370 was transferred via thetransfer set to empty sterile, single use only syringes on automatedpower injectors. Chemical integrity was maintained throughout anextended hold period for the bottle of Isovue once the container closurewas penetrated. Confirmation of chemical integrity includeddemonstration that the fluid samples exhibited sub-visible and visibleparticles within tolerance limits. Confirmation of chemical integrityalso included a demonstration that the fluid samples lacked leachablecompounds at levels of potential toxicological concern.

Example 2 Microbial Ingress Resistance

A microbial ingress resistance study was performed to verify the abilityof a Bracco transfer set [part no. 100115] similar to that shown in FIG.2 and a multi-dose, multi-patient Isovue contrast media container toresist microbial ingress into fluid pathways under simulated operatingconditions. The Bracco transfer set was configured as a disposablecomponent intended to be used to fill injector syringes, such asinjector syringes of the Bracco Empower CTA® and Medrad Stellant®injectors, with Isovue contrast media from the multi-dose, multi-patientcontainers.

To perform the testing, the injection systems were set up and operatedusing disposables that were surface contaminated (e.g., challenged) atspecified locations (e.g., contact points) with a high concentration ofviable microorganisms (10 μl of a ≧1,000 colony forming units permilliliter [CFU/mL]) and allowed to dry (<90 minutes). In particular,the disposables were challenged by applying a high concentrationmicroorganism to each of the following contact points: a center of aseptum of the multi-dose, multi-patient Isovue container; a side surfaceof a spike guard of the transfer set, around the base of the bottlespike; a Luer connection of the transfer set; and an exterior base ofsyringe tip. Using new, sterile disposables each time, individual testswere performed using each of the following bacteria: Staphylococcusaureus, Staphylococcus epidermidis, Pseudomanas aeruginosa, andKlebsiella pneumonia.

After allowing the bacteria to dry, the challenged contact points of thetransfer set and the Isovue container septa were decontaminated with analcohol wipe. The injectors were then set up and operated in accordancewith the operator's manual for each injector system. Aliquots of thefluid that would normally be injected into a patient were collected froma distal end of a discharge line (e.g., patient line) attached to theinjector syringe. Injection samples were dispensed at 0, 4, 10 and 14hours after connection and assayed for sterility. In addition, a sampleof the remaining contrast in the bottle at the end of the 14 hourtesting protocol was collected and evaluated for sterility.

The results of the sterility testing are provided in Tables 3 and 4below.

TABLE 3 Challenge Site Staphylococcus epidermidis Klebsiella pneumoniaeSite Description # Tests Results # Tests Results Center of septum of thebottle cap 4 replicates of No 4 replicates of No each set: Growth eachset: Growth T = 0 hr. in T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20 T= 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr. Bottle BottleFor a total of For a total of 20 samples 20 samples Side surface of thespike guard of the 4 replicates of No 4 replicates of No transfer set,around the base of the each set: Growth each set: Growth bottle spike T= 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20 T = 10 hr.samples T = 10 hr. samples T = 14 hr. T = 14 hr. Bottle Bottle For atotal of For a total of 20 samples 20 samples The Luer connection of thetransfer 4 replicates of No 4 replicates of No set each set: Growth eachset: Growth T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20T = 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr. BottleBottle For a total of For a total of 20 samples 20 samples The exteriorbase of the syringe tip 4 replicates of No 4 replicates of No each set:Growth each set: Growth T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T =4 hr. 19/19 T = 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr.Bottle Bottle For a total of For a total of 20 samples 19 samplesOVERALL: No growth in 319 No growth in 80 of 80 No growth in 79 of 79samples including 80 samples samples, including 20 samples, including 20from the Isovue multidose, samples from the Isovue samples from theIsovue multipatient bottle at the end of 14 multidose, multipatientmultidose, multipatient hours. bottle at the end of 14 bottle at the endof 14 hours. hours.

TABLE 4 Challenge Site Staphylococcus aureus Pseudomonas aeruginosa SiteDescription # Tests Results # Tests Results Center of septum of thebottle cap 4 replicates of No 4 replicates of No each set: Growth eachset: Growth T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20T = 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr. BottleBottle For a total of For a total of 20 samples 20 samples Side surfaceof the spike guard of the 4 replicates of No 4 replicates of No transferset, around the base of the each set: Growth each set: Growth bottlespike T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20 T = 10hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr. Bottle Bottle For atotal of For a total of 20 samples 20 samples The Luer connection of thetransfer 4 replicates of No 4 replicates of No set each set: Growth eachset: Growth T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T = 4 hr. 20/20T = 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr. BottleBottle For a total of For a total of 20 samples 20 samples The exteriorbase of the syringe tip 4 replicates of No 4 replicates of No each set:Growth each set: Growth T = 0 hr. for T = 0 hr. for T = 4 hr. 20/20 T =4 hr. 20/20 T = 10 hr. samples T = 10 hr. samples T = 14 hr. T = 14 hr.Bottle Bottle For a total of For a total of 20 samples 20 samplesOVERALL: No growth in 319 No growth in 80 of 80 No growth in 80 of 80samples including 80 samples samples, including 20 samples, including 20from the Isovue multidose, samples from the Isovue samples from theIsovue multipatient bottle at the end of 14 multidose, multipatientmultidose, multipatient hours. bottle at the end of 14 bottle at the endof 14 hours. hours.

The result demonstrated that the Isovue multi-dose, multi-patientcontainer, when used with the Bracco transfer set to fill empty sterilesyringes on syringe-based injectors, effectively resisted microbialingress into the fluidic pathway.

Example 3 Cross-Contamination

A cross-contamination study was performed to verify the ability of aBracco transfer set similar to that shown in FIG. 3 to avoidcross-contamination between the patient-specific fluid transfercomponents (identified as the “patient set” in FIG. 3) and the multi-usefluid transfer components (identified as the “day set” in FIG. 3). TheBracco transfer set was configured to transfer medical fluid frommulti-dose, multi-patient containers using a fluid pressurizationsystem, such as the Bracco CT Exprès™ system.

To perform the testing, a Bracco CT Exprès™ system was set-up asoutlined in the operator's manual. This involved attaching a day set anda patient set to the system as well as installing a multi-dose containerof saline. The fluid transfer components of the system, including theday set and patient set, were then primed with saline from themulti-dose container by operating the peristaltic pump of the system todraw fluid from the container and discharge the fluid through the dayset and the patient set.

After priming the fluid transfer components, the patient set (PS #1) wasejected from the system and a new patient set (PS #2) was installed andmanually primed with saline just past the cassette rollers of theperistaltic pump. The patient set (PS #2) was then clamped adjacent theperistaltic pump and a syringe needle inserted into the patient settubing, filling the patient set tubing with red no. 40 dye. The distalend of the patient set (PS #2) tubing was then raised to a height 21 cmabove the rest of the patient set. The clamp was then opened and the redno. 40 dye allowed to sit in the tubing for 40 minutes, open toatmospheric pressure at the distal end and the peristaltic pump at theopposite end.

After the 40 minute hold time, the patient set tubing was double clampedonce just past the peristaltic pump and once approximately 5 cm awayfrom the first clamp. The patient set (PS #2) was then removed from thesystem and a new patient set (PS #3) installed onto the system. Theperistaltic pump was then operated to eject approximately 4 millilitersof solution from each of a first (left side) bottle of contrast, asecond (right side) bottle of contrast, and a bag of saline. The sampleswere collected from the distal end of the patient set (PS #3). Inaddition, a fourth sample was collected by cutting the removed patientset (PS #2) between the two clamps and extracting fluid from the portionof tube between the clamps.

The samples were analyzed in triplicate at 506 nm to determine if anyred no. 40 dye was present in the samples. The results of thecross-contamination testing are provided in Tables 5 and 6 below.

TABLE 5 Mean Absorbance of Samples [Range is across 9 readings (3 tests(left contrast bottle, right contrast bottle, and Sample ID saline bag)with 3 readings per test] Replicate 1 0.000 [−0.002-0.001]   Replicate 2−0.001   [−0.002-0.000]   Replicate 3 0.000 [−0.001-0.001]   Replicate 40.000 [−0.001-0.001]   Replicate 5 0.000 [0.000-0.000] Replicate 6 0.000[0.000-0.000] Replicate 7 −0.001   [−0.001-0.000]   Replicate 8 −0.001  [−0.001-0.000]   Replicate 9 0.000 [0.000-0.001] Replicate 10 0.000[0.000-0.000] Replicate 11 0.001 [0.000-0.002] Replicate 12 0.001[0.000-0.002] Replicate 13 0.001 [0.001-0.001] Replicate 14 0.000[0.000-0.000]

TABLE 6 Mean Absorbance of Challenged Red No. 40 Dye CalculatedConcentration [Range is across 3 readings [Concentrated dye was SampleID (1 test in triplicate)] diluted 100,000 fold] Replicate 1 0.056 0.248[0.055-0.057] Replicate 2 0.057 0.253 [0.0556-0.058]  Replicate 3 0.0540.240 [0.053-0.055] Replicate 4 0.058 0.257 [0.058-0.059] Replicate 50.059 0.262 [0.059-0.059] Replicate 6 0.047 0.208 [0.047-0.047]Replicate 7 0.053 0.235 [0.052-0.053] Replicate 8 0.054 0.240[0.054-0.055] Replicate 9 0.050 0.222 [0.050-0.050] Replicate 10 0.0550.244 [0.055-0.056] Replicate 11 0.056 0.248 [0.056-0.057] Replicate 120.058 0.257 [0.058-0.059] Replicate 13 0.053 0.235 [0.053-0.053]Replicate 14 0.041 0.182 [0.041-0.042] Average 0.054 0.239

The result demonstrated that the Bracco transfer set, when used todispense fluid from multi-dose, multi-patient containers using theBracco CT Exprès™ system, effectively resisted cross-contaminationbetween the patient set and the day set.

The invention claimed is:
 1. A method comprising: providing a fluiddelivery system that includes a medical fluid container, a fluidpressurizing unit, and a fluid transfer set, wherein the fluid transferset is connected to transfer a fluid from the medical fluid container tothe fluid pressurizing unit; drawing the fluid from the medical fluidcontainer, through the fluid transfer set, and into the fluidpressurizing unit so that the fluid transfer set and fluid pressurizingunit are filled with the fluid; placing a discharge outlet of the fluidpressurizing unit in fluid communication with a fluid reservoircontaining a tracking fluid, wherein the tracking fluid contains atracking agent, and wherein the fluid reservoir is closed so that thefluid pressurizing unit cannot draw the fluid from the medical fluidcontainer and discharge the fluid into the fluid reservoir; operatingthe fluid pressurizing unit so as to pressurize a portion of the fluidin the fluid pressurizing unit; extracting one or more samples of thefluid from at least one of the medical fluid container, the fluidtransfer set, and the fluid pressurizing unit; and analyzing the one ormore samples to determine a concentration of the tracking agent in theat least one of the medical fluid container, the fluid transfer set, andthe fluid pressurizing unit.
 2. The method of claim 1, wherein the fluidtransfer set comprises a polymeric tube that extends from a proximal endto a distal end and includes a bottle spike positioned on the proximalend of the polymeric tube and a mechanical connector positioned on thedistal end of the polymeric tube.
 3. The method of claim 1, wherein thepressurizing unit comprises one of a syringe and a peristaltic pump. 4.The method of claim 1, wherein the tracking agent is not present in thefluid from the medical fluid container and includes one of a dye, abacterium, and a virus.